Drug delivery composition comprising polymer-lipid hybrid microparticles
A dry composition, comprising three-dimensional porous microparticles, wherein the microparticles comprise: (i) an active substance (eg a poorly water soluble drug), (ii) polymeric nanoparticles such as those composed of a biocompatible and/or biodegradable polymer (eg a PLGA polymer) (iii) lipid droplets (eg droplets of a medium chain triglyceride (MCT)), (iv) a nanoparticle stabilizing agent such as PVA or DMAB, and optionally, (v) a cryoprotectant (eg mannitol); wherein said active substance is carried by said nanoparticles and/or lipid droplets. The composition of the present invention may be formulated into, for example, a medicament for the treatment and/or prevention of various diseases or disorders (eg human or veterinary therapeutics). The average diameter of the individual microparticles of the composition, may be in the order of 2.5-3.5 μm which are particularly suitable for administration to the lung.
1. A dry composition comprising three-dimensional porous microparticles, wherein said microparticles comprise: (i) an active substance, (ii) polymeric nanoparticles, (iii) lipid droplets, (iv) a nanoparticle stabilising agent, and (v) a cryoprotectant; wherein said active substance is carried by said nanoparticles and/or lipid droplets; wherein the composition comprising 1 to 5 wt % of the active substance, 25 to 50 wt % of the polymeric nanoparticles, 25 to 50 wt % of lipid droplets, 1 to 25 wt % of the nanoparticle stabilising agent, and 1 to 10 wt % of the cryoprotectant based on the total weight of the composition; wherein the cryoprotectant is selected from the group consisting mannitol, lactose, trehalose, sucrose, glucose, fructose and sorbitol.
2. The composition of claim 1 , wherein the active substance is a pharmaceutical agent.
3. The composition of claim 2 , wherein the pharmaceutical agent is a poorly water soluble drug.
4. The composition of claim 1 , wherein the polymeric nanoparticles comprise a biocompatible and/or biodegradable polymer.
5. The composition of claim 4 , wherein the polymeric nanoparticles comprise a PLGA polymer.
6. The composition of claim 1 , wherein the lipid droplets comprise a medium chain triglyceride (MCT).
7. The composition of claim 1 , wherein the nanoparticle stabilising agent is selected from poly vinyl alcohol (PVA) and didodecyldimethyl ammonium bromide (DMAB).
8. The composition of claim 1 , wherein the microparticles do not consist of a lipid shell-polymer nanoparticle core architecture.
9. The composition of claim 1 produced by a method comprising spray drying an oil in water (o/w) emulsion comprising lipid droplets and polymeric nanoparticles in the aqueous phase.
10. The composition of claim 1 , wherein the microparticles have an average diameter of <5 μm.